Potassium uptake into astrocytes in primary cultures was measured by the aid of 42K. Acute application of lithium in concentrations of 1 and 5 mM, but not 0.5 und 0.25 mM, exerted a significant inhibition of the potassium uptake rates. This effect is due to a partial impairment of the ouabain-sensitive part of the uptake into the cells caused by a lithium interaction with the extracellular K+-activated site of the Na+, K+-ATPase. After 14 days of exposure of the astrocytes to 1 mM lithium, the potassium uptake remained lower in the presence of lithium than in its absence. However, the cells had adjusted to the chronic presence of lithium by increasing their potassium uptake to such an extent that, during the exposure to 1 mM lithium, it was indistinguishable from that in cultures from the same batches grown in the absence of lithium and measured in the absence of this compound. The interference by lithium with potassium uptake into astrocytes may well be related to the inhibition of potassium clearance in the CNS described in the literature.